“Why do people age, there is no limit to the life span of people?” “Can we achieve a long-lived, old-fashioned child? “Two years ago, Cai Shiqing, a researcher at the Center for Excellence in Brain Science and Intelligent Technology at the Chinese Academy of Sciences, raised these questions at a popular science forum, drawing the attention and questions of many peers, and his views were summed up by some as “human beings are on track to achieve a lifetime, and our goal is ‘not old'”.
“Old and Old” Effect Synthesis
Pictured is researcher Cai Shiqing
Scientists discover new anti-aging target gene For Brain Science and Intelligent Technology Excellence Innovation Center of the Chinese Academy of Sciences
Now, the scientific research team led by Cai Shiqing and the Jiang Lubin research team of the Pasteur Institute in Shanghai, Chinese Academy of Sciences, have worked together for many years to make a new breakthrough on this issue: they have discovered new anti-aging target genes, and accordingly illustrate the regulatory mechanism of cognitive aging, providing new clues to the realization of “healthy aging”. The paper on the results was published online in the international academic journal Nature.
“Each of us has a close relationship with aging, from birth to adulthood, to age, in the process of the later, the physiological functions will slowly degrade, and even some geriatric diseases, aging is also the biggest risk factor for old age disease.” Cai Shiqing in an interview with reporters, said that the results released after the most attention, or health and longevity of the eternal topic of human beings. So, can human beings use scientific means to lift the veil of aging, to fight the years in the face carved in the road wrinkles of the “pig knife”, and can resist the disease accompanied by aging, and even “old and unfailing”?
“Long-lived” and “not old”
Although people have been pursuing the pursuit of long-term life for thousands of years, the modern sense of scientific research on aging is not too long. According to Yuan Jie, the first author of the paper and a doctoral student at the Center for Excellence in Brain Science and Intelligent Technology at the Chinese Academy of Sciences, the key starting point for aging research was in the late 1930s, when scientists found that restricting diet sedated the life span of mice and rats, to some extent indicating that “aging is a malleable process.”
With the emergence of new experimental methods, people have further understanding of the phenomenon of aging from the individual to the cellular and molecular level, scientists have put forward a number of theories to try to explain aging. In the 1990s, with the development of molecular biology, the study of aging entered the genetic age, and there was a causal relationship between genes and aging.
In a typical achievement, in 1983, a scientist identified the first longevity mutation in an experimental animal nematode, a genetic mutation called age-1, which extended nematode life by 40-60 percent. The discovery surprised many scientists: A mutation in a gene can change the length of life.
Over the next few decades, scientists have discovered hundreds of genes that can extend their lives, and have learned more about the biological mechanisms of longevity.
One interesting finding is that some longevity genes, while “prolonging life”, do not necessarily “delay the degradation of behavioral function and cognitive function”. For example, as older people age, their mobility declines, and the incidence of degenerative diseases associated with aging, such as Alzheimer’s disease, cancer, Parkinson’s disease, and diabetes, increases significantly.
Yuan Jie said that from the first discovery that life expectancy is determined by genes, to the past few decades, researchers have found many genes and genetic pathways that can affect life expectancy, but in recent years it has been found that longer life expectancy does not mean an improvement in behavior and health, for “the mechanism of behavioral degradation in the aging process.” What the hell is that people don’t study enough.
In fact, when it comes to aging research, many people immediately think of “long-lived” and “not old” meaning different: the former refers to longer life, while the latter refers to the maintenance of youthful vitality, for example, at the age of 50 can have 30 years of age appearance, at 70 can also be like 40 or 50 years old, can still jump like 40 or 50 years old Not only that, “long life” “not old” both in biology, but also by different mechanisms.
Yuan Jie said that compared to maintaining a weak and sick life in the middle of the wind and candle, people want to improve the quality of life in old age, to achieve “old and unfailing.” Therefore, how to reduce the incidence of geriatric diseases after human aging, to understand the “old and unfailing” biological mechanism, is a difficult problem before the scientific community.
“Looking for the real killer”
To understand the mechanisms of behavioral degradation, we need to find genes that control behavioral degradation. But the genes in the organism thousands, to find the “true murder”, its difficulty can be called “needle in a haystack.”
In biology, Yuan said, in order to study the function of a gene, it can be removed from the genome to observe what abnormalities occur in the organism, so as to speculate on what physiological function the gene has in the organism.
Of course, this process is usually done in experimental animals , not humans. The study chosen by Cai’s team was an experimental animal called nematodes.
Cai Shiqing told reporters that the length of only about 1 mm of small worms, three or four days can mature to produce offspring, the entire life cycle is only about 3 weeks, behavior is not complex, but there is a clear aging performance, coupled with the animal’s genetic background is clear, is a biologist study of aging commonly used animal models.
Of course, even in online bugs, it’s not easy to detect behavioral changes in the aging process. Is there a biological marker that facilitates tracking, reflects the degradation of behavioral functions, and is suitable for large-scale screening? Cai Shiqing’s team came up with a neurotransmitter system.
The so-called neurotransmitter system is a chemical that transmits signals between neurons in the brain. Yuan Jie said that in the process of aging organisms, neurotransmitter function once abnormal, will lead to behavioral function degradation, and improve the neurotransmitter function, can improve the behavior of the elderly.
According to Yuan Jie, if the neurotransmitter function changes as an indicator, at the whole genome level screening, looking for genes to regulate aging, you can obtain the corresponding candidate genes. In this way, the team found 59 candidate genes: 10 of which have been reported to be associated with degenerative diseases or cell aging, while the remaining 49 are the first to be found to affect the aging process.
Next, the team built a network of interactions between these candidate genes, and they noticed two genes at key nodes in the network: BAZ-2 and SET-6. Interestingly, the mutant nematodes, which are missing both genes, have a much slower rate of aging and degrade with other wild nematodes, while also extending their lifespan.
“This is a very reassuring result, indicating that the screening system we designed is very effective. Yuan Jie said that this result shows that BAZ-2 and SET-6 genes are accelerated aging, and correspondingly, artificially reduce the function of these two genes, can delay aging.
Is it the same for people?
Of course, this is only the result of scientists’ experiments on nematodes, and does the human body have similar anti-aging genes?
The team further studied BAZ-2 and SET-6, two potential anti-aging targets, and found their corresponding human homologous genes, BAZ2B and EHMT1, respectively. So, these two genes must be anti-aging, researchers need to do further verification.
At this point, an experimental animal that is more complex than nematodes but closer to human kinship came on the scene — mice. The researchers built mice with the BAZ2B gene to test the gene’s anti-aging mechanism.
“The life cycle of mice takes up to three years, from starting to build genes to knock out mice, to removing background mutations, and finally growing mice to ‘old age’, which takes three years. Cai Shiqing said that Kung Fu is not responsible for people, after a long experiment, the researchers got a “surprise discovery” –
Wild mice are “middle-aged, ” while BAZ2B-knocked mice are able to maintain a slimmer figure during the aging process. What’s more, behavioral tests showed that older BAZ2B knockout mice maintained better cognitive abilities than wild mice.
“This suggests that BAZ2B also regulates the aging process in mammals and is a new anti-aging target gene. In the same way, They also validated the mechanism of action of another human homologous gene, EHMT1, Cai said.
“It’s a whole new discovery. The discovery of these genes provides the basis for a further comprehensive study of the mechanisms of behavioral degradation in the aging process, said the author of the study in the journal Nature.
More to be expect, these two genes, BAZ2B and EHMT1, are likely to be targets for anti-aging drugs. On this basis, the team began to explore changes in Alzheimer’s disease in the two anti-aging target genes, and found that in alzheimer’s patients, the expression of BAZ2B and EHMT1 was positively correlated with the disease’s progression and negatively associated with the expression of key mitochondrial proteins, Cai said.
“These results suggest that increased expression in the aging brain by BAZ2B and EHMT1 may be a major cause of mitochondrial function deficiency in Alzheimer’s disease. This means that they can be used as a target gene for anti-aging drugs, Cai said.
But he also said that the study also has some limitations: behavioral testing and mechanism research is only nematodes, mice, not on human verification, given that humans and nematodes, mice and other experimental organisms there are large species differences, whether these studies can be applied in humans, there is still a lot of uncertainty.
It also means that there is still a long way to go from scientific research to clinical applications. “Our work is the first time in the world that we have studied healthy aging from the perspective of differences in individual aging speeds, providing a new perspective for anti-aging research,” Cai said. Further research is needed as to whether these genes have the same function in humans. “